According to the National Center for Cultural Competence (link is external), “cultural influences” refer to the beliefs, values, traditions, and practices of a culture that, in the context of health care and medicine, define the health-related needs of individuals, families, and communities. These include the culturally based belief systems of the etiology of illness and disease, those related to health and healing, and attitudes toward seeking help from health care providers. The NIH Office of Behavioral and Social Sciences Research says, “Social and cultural factors influence health by affecting exposure and vulnerability to disease, risk-taking behaviors, the effectiveness of health promotion efforts, and access to, availability of, and quality of health care.”
Extramural research is NIH-funded research by way of awards, grants, and contracts to outside institutions to help them pay for research projects and resources. This funding includes the salaries of the investigators they employ, proportional to the percentage of their time on the particular research project. See http://www.niaid.nih.gov/researchfunding/qa/pages/extraintra.aspx#difference.
Inclusion of Women
The term “inclusion of women” refers to the legal requirement set forth in the National Institutes of Health Revitalization Act of 1993 (link is to an external PDF) (PDF, 109KB) that women must be included as subjects in clinical research. This requirement pertains to all clinical research funded by NIH unless the research “is inappropriate with respect to the health of the subjects,” “is inappropriate with respect to the purpose of the research,” or “is inappropriate under such other circumstances as the Director of NIH may designate.”
The current NIH definition of clinical research is human subjects research that is:
- Patient-oriented research. Research conducted with human subjects (or on material of human origin, such as tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that use human tissues that cannot be linked to a living individual. This definition includes (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, or (d) development of new technologies.
- Epidemiologic and behavioral studies.
- Outcomes research and health services research.
Note: Studies falling under 45 CFR 46.101(b) (4) (Exemption 4) are not considered clinical research under this definition.
In October 2014, NIH revised its definition of clinical trial to more clearly distinguish between clinical trials and clinical research studies and to enhance the precision of the information that NIH collects, tracks, and reports on clinical trials. The current definition of a clinical trial is:
A research study22 in which one or more human subjects23 are prospectively assigned24 to one or more interventions25 (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.26
Phase III Clinical Trial—Further Clarification
As previously described, NIH policy places specific requirements on investigators whose applications seek funding for Phase III clinical trials, as legally required by 42 USC 289a-2.
For the purpose of NIH policies, an NIH-defined Phase III clinical trial (link is to an external PDF) (PDF, 251KB) is:
A broadly based prospective Phase III clinical investigation, usually involving several hundred or more human subjects, for the purpose of evaluating an experimental intervention in comparison with a standard or control intervention or comparing two or more existing treatments. Often the aim of such investigation is to provide evidence leading to a scientific basis for consideration of a change in health policy or standard of care. The definition includes pharmacologic, nonpharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included.
Inclusion of Women and Minorities as Participants in Research Involving Human Subjects—Policy Implementation Page NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research—Amended, October 2001 Consideration of Sex as a Biological Variable in NIH-funded Research Enrolling Pregnant Women: Issues in Clinical Research
- See Common Rule definition of research at 45 CFR 46.102(d).
- Common Rule definition of human subject at 45 CFR 46.102(f).
- The term prospectively assigned refers to a pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, other control) of a clinical trial.
- An intervention is defined as a manipulation of the subject or the subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include drugs/small molecules/compounds, biologics, devices, procedures (e.g., surgical techniques), delivery systems (e.g., telemedicine, face-to-face interviews), strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits), treatment strategies, prevention strategies, and diagnostic strategies.
- Health-related biomedical or behavioral outcome is defined as the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life. Examples include positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression), positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers, reading comprehension and/or information retention), positive or negative changes to disease processes, positive or negative changes to health-related behaviors, and positive or negative changes to quality of life.